Vitamin D3 vs Vitamin K2 (MK-7)

Mechanism

Vitamin D3 (cholecalciferol) is hydroxylated in the liver to 25(OH)D (calcidiol), then in the kidneys to 1,25(OH)2D (calcitriol), the active hormone. Calcitriol binds the nuclear vitamin D receptor (VDR), forming a heterodimer with RXR that regulates >1000 genes. Key actions: upregulation of intestinal calcium/phosphorus absorption (TRPV6, calbindin), modulation of innate immunity (cathelicidin LL-37 antimicrobial peptide production), suppression of adaptive immune overactivation (Th1/Th17 to Treg shift), regulation of PTH and osteocalcin for bone mineralization, and modulation of insulin secretion from beta cells.

Standard Dosing

5000 IU daily (125 mcg)

Timing

With largest fat-containing meal of the day (fat-soluble). Morning preferred.

Cycle Duration

ongoing (lifelong for most people in northern latitudes)

Side Effects

• Hypercalcemia at excessive doses (>10,000 IU/day long-term without monitoring)
• Nausea/vomiting (toxicity)
• Kidney stones (with excessive calcium)
• Metallic taste (toxicity sign)

Contraindications

• Hypercalcemia
• Granulomatous diseases (sarcoidosis, some lymphomas — unregulated 1-alpha hydroxylase conversion)
• Primary hyperparathyroidism (without monitoring)
• Williams syndrome

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Mechanism

Vitamin K2 (menaquinone-7) activates vitamin K-dependent proteins via gamma-carboxylation of glutamic acid residues. Key targets: osteocalcin (directs calcium into bone matrix), matrix Gla protein (MGP, inhibits arterial calcification), Gas6 (cell signaling, neuroprotection), and protein S (anticoagulant). MK-7 has a long half-life (~72 hours vs 1-2 hours for K1) enabling consistent carboxylation activity with once-daily dosing. It works synergistically with Vitamin D3 to regulate calcium metabolism — D3 increases calcium absorption while K2 directs its deposition.

Standard Dosing

100-200 mcg MK-7 daily

Timing

With fat-containing meal alongside Vitamin D3.

Cycle Duration

ongoing (mandatory co-supplement with Vitamin D3)

Side Effects

• Generally very well tolerated
• Rare: mild GI discomfort
• Theoretical thrombotic risk in deficiency-rebound scenario (unproven)

Contraindications

• Warfarin/coumarin anticoagulant therapy (unless specifically directed by physician with INR monitoring)

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